What is the recommended workup and treatment for a patient with suspected secondary hypertension?

Workup for Secondary Hypertension

When to Screen for Secondary Hypertension

Screen for secondary hypertension only in patients with specific clinical clues, as it affects 5-10% of all hypertensive patients but increases to 10-20% in resistant cases. 1, 2

Key indications for screening include:

• Age of onset <30 years (or <40 years per ESC 2024) or new onset after age 50 1, 3
• Resistant hypertension (BP >140/90 mmHg despite optimal doses of ≥3 antihypertensive drugs including a diuretic) 1, 2
• Abrupt onset or sudden deterioration of previously controlled hypertension 1, 2
• Hypertensive urgency or emergency 1
• Target organ damage disproportionate to duration or severity of hypertension 1

Initial Laboratory and Diagnostic Workup

Basic Screening for All Suspected Cases

All patients with suspected secondary hypertension should undergo basic laboratory screening before expensive imaging studies. 1

Required initial tests include:

• Serum creatinine and eGFR 4, 1
• Urinalysis and urinary albumin-to-creatinine ratio 4, 1
• Serum sodium and potassium 1, 2
• Fasting blood glucose or HbA1c 1, 2
• Thyroid-stimulating hormone (TSH) 1, 2
• 12-lead ECG 4, 1

Revolutionary Change in Screening Approach

The ESC 2024 guidelines now recommend measuring plasma aldosterone-to-renin ratio in ALL adults with confirmed hypertension (Class IIa recommendation), representing a major shift from traditional selective screening. 1 This reflects growing recognition that primary aldosteronism affects 8-20% of resistant hypertension cases and is significantly underdiagnosed. 1, 2

Targeted Investigations Based on Clinical Suspicion

Primary Aldosteronism (Most Common Treatable Cause)

Clinical clues suggesting primary aldosteronism:

• Resistant hypertension with spontaneous or diuretic-induced hypokalemia 1, 2
• Muscle cramps or weakness 1
• Family history of early-onset hypertension or stroke at young age 1, 2

Diagnostic workup:

• Plasma aldosterone-to-renin ratio (ARR) as initial screening test (high negative predictive value; ratio >20 with elevated aldosterone and low renin is suggestive) 1, 2
• Confirmatory testing with IV saline suppression test or oral sodium loading test 1, 2
• Adrenal CT scan for localization 1, 2
• Adrenal vein sampling for lateralization before surgery 1, 2

Renovascular Disease

Clinical clues suggesting renovascular disease:

• Abrupt onset or worsening hypertension 1, 2
• Flash pulmonary edema 1
• Abdominal bruits 2, 3
• Early-onset hypertension in women (suggests fibromuscular dysplasia) 1

Diagnostic workup:

• Renal ultrasound with Duplex Doppler as initial test 1, 2
• CT or MR renal angiography for confirmation 1, 2

Obstructive Sleep Apnea (Highly Prevalent in Resistant Hypertension)

Clinical clues suggesting obstructive sleep apnea:

• Present in 25-50% of resistant hypertension cases 1
• Snoring, daytime sleepiness, obesity 1
• Non-dipping nocturnal BP pattern on ambulatory monitoring 1

Diagnostic workup:

• Home sleep apnea testing or polysomnography 1, 2

Pheochromocytoma (Rare but Dangerous)

Clinical clues suggesting pheochromocytoma:

• Episodic symptoms (headaches, palpitations, sweating) 1
• Labile hypertension 1

Diagnostic workup:

• 24-hour urinary catecholamines or metanephrines 1
• Plasma metanephrines (only when specifically suspected based on clinical features) 1
• Abdominal/adrenal imaging after biochemical confirmation 1

Renal Parenchymal Disease

Clinical clues suggesting renal parenchymal disease:

• History of urinary tract infections, obstruction, hematuria 1
• Urinary frequency, nocturia 1
• Family history of polycystic kidney disease 1

Diagnostic workup:

• Elevated creatinine, reduced eGFR 4, 1
• Abnormal urinalysis with proteinuria or hematuria 4, 1
• Renal ultrasound 1

Cushing's Syndrome

Clinical clues suggesting Cushing's syndrome:

• Truncal obesity, purple striae, fatty deposits 1, 3
• Hyperglycemia 3

Coarctation of the Aorta

Clinical clues suggesting coarctation:

• Radio-femoral delay, decreased femoral pulses 1, 3
• Hypertension in young patients 3

Additional Diagnostic Studies When Indicated

Echocardiography is recommended in patients with ECG abnormalities or signs/symptoms of cardiac disease to assess for left ventricular hypertrophy, aortic coarctation, and cardiac dysfunction. 4, 1

Fundoscopy is recommended if BP >180/110 mmHg to evaluate for retinal changes, hemorrhages, and papilledema in hypertensive emergency. 4, 1

Critical Pitfalls to Avoid

Do not perform expensive imaging studies before completing basic laboratory screening. 1 This wastes resources and delays diagnosis.

Consider medication-induced hypertension before extensive workup. 1 Many drugs can cause or worsen hypertension.

Interpretation of aldosterone-to-renin ratio can be affected by antihypertensive medications: mineralocorticoid receptor antagonists raise aldosterone levels, while beta-blockers and direct renin inhibitors lower renin levels. 1 Ideally, discontinue interfering medications before testing when safe to do so.

Delayed diagnosis leads to irreversible vascular remodeling, resulting in residual hypertension even after treating the underlying cause. 1, 5 Early detection and treatment are crucial to prevent permanent vascular and target organ changes.

Secondary hypertension is significantly underrecognized despite affecting 5-10% of all hypertensive patients. 1, 2 Maintain high index of suspicion in appropriate clinical scenarios.

Referral to specialized centers with appropriate expertise is recommended for complex cases requiring advanced diagnostic procedures like adrenal vein sampling or renal angiography. 1